Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as depot medroxyprogesteroneacetate(DMPA) are considered the hormonal contraceptives of choice during all stages of lactation. Fair quality evidence indicates that DMPA does not adversely affect the composition of milk, the growth and development of the infant, or the milk supply. Some evidence indicates that progestin-only contraceptives may offer some protection against bone mineral density loss during lactation, or at least not exacerbate it.
The timing of initiation of DMPA is controversial. The product labeling states that it should be started no sooner than 6 weeks postpartum, based on data submitted for product approval. Studies of fair quality seem to indicate that concerns about immediate adverse effects on the infants is unfounded; however, starting sooner theoretically could affect the newborn infant adversely because of slower metabolism of the drug than older infants. Of concern is that no data exist on the effects of progesterone on brain and liver development at this age. Administration sooner than 6 weeks postpartum could interfere with the exclusivity or duration of lactation. A systematic review of studies using early postpartum initiation of DMPA concluded that all of the studies were of low quality and inadequate to disprove the concern about DMPA's effects on milk production if given sooner than 6 weeks after delivery.
Based on the available evidence, expert opinion in the United States holds that the advantages of using progestin-only contraceptive products generally outweigh the theoretical or proven risks before 4 weeks postpartum. However, is prudent to give it no sooner than 3 days postpartum when lactation is established.
Seven women were given a single intramuscular dose of depot medroxyprogesteroneacetate150 mg 1 week after delivery. Peak milk levels occurred at varying times between days 8 to 28 after the injection, with most between 1 and 2 weeks. Peak levels ranged from 1.3 to 2.3 mcg/L. In 3 women, levels were measured 50 to 87 days after the dose and were still detectable in milk in the range of 0.54 to 0.98 mcg/L.
Ten women received a single dose of depot medroxyprogesteroneacetate150 mg at 6 to 7 weeks postpartum. Breastmilk levels were measured weekly for 12 weeks. Average milk levels were highest at 1 week after injection at about 7.5 mcg/L and gradually fell to about 0.5 mcg/L at 12 weeks after the injection. The authors estimated that a breastfed infant would receive 1 to 13 mcg/day at 1 week after injection, 0.2 to 1.5 mcg/day 8 weeks after injection and up to 1 mcg/day at 12 weeks after injection.
Thirteen male infants whose mothers received 150 mg of medroxyprogesteroneacetateintramuscularly at weeks 6 and 18 postpartum were breastfed. Complete 4-hour urine specimens were collected on 20 occasions during maternal treatment, including on the days after the injection known to have high maternal serum levels. No medroxyprogesterone or metabolites were detected by GC-MS assay (lower limit not specified) in the urine of the infants.
Effects in Breastfed Infants:
In a nonrandomized study, 228 women chose depot medroxyprogesteroneacetateinjection every 3 months as a postpartum contraceptive starting in months 2 to 4 postpartum. Eighty-eight percent of the women breastfed their infants for at least 6 months. Infants were examined during the study and again at age 4.5 years. No adverse effects on infant growth and development were noted in the exposed infants.
One follow-up study of 1215 children whose mothers received depot medroxyprogesterone during nursing reported a delayed appearance of pubic hair (reported by mothers) in pubescent girls, but not boys. No other effects on growth were observed after correction for socioeconomic status.
A multicenter, nonrandomized study followed 541 infants whose mothers received depot medroxyprogesteroneacetateinjection 150 mg every 3 months for contraception during breastfeeding. No adverse effects on infant growth through the first year were found in comparison to standard measurements.
Thirteen male breastfed infants whose mothers received 150 mg of medroxyprogesteroneacetateintramuscularly at weeks 6 and 18 postpartum were studied. No differences were found in serum levels of luteinizing hormone, follicle-stimulating hormone, unconjugated testosterone, or cortisol compared to those of a group of 9 control infants.
In a nonrandomized study comparing 190 infants of women using depot medroxyprogesterone to those using a nonhormonal contraceptive or no contraception starting at about day 57 postpartum, no difference in infant growth rates were seen from birth to 6 months of age, regardless of whether the infant was fully or partially breastfed.
In a retrospective cohort study of 270 infants whose mothers were given DMPA postpartum, no effect of DMPA on weight when adjusted for cofounders and no differences between groups in psychomotor development, milestones, health problems, infant height or physical examinations.
A non-blinded, randomized study of exclusively breastfeeding women compared those who received an etonogestrel implant 24-48 hours after delivery (n = 20) to those who received a 150 mg depot medroxyprogesteroneacetateinjection at 6 weeks postpartum (n = 20). No difference in infant weight gain was noted between the two groups.
Possible Effects on Lactation:
Galactorrhea has been reported in nonpregnant, nonlactating women using depot medroxyprogesteroneacetate(DMPA). In one case series, 3.6% of 360 adolescents who used depot medroxyprogesteroneacetateas a contraceptive for at least 6 months developed galactorrhea with normal prolactin levels.
Numerous studies found that the use of intramuscular depot medroxyprogesteroneacetateas a contraceptive beginning at 7 days postpartum or later either has no negative effect or causes increases in the milk supply, duration of lactation or quality of breastmilk. However, most of these were so seriously flawed that no valid conclusion can be drawn on the effect of early initiation on breastfeeding duration.
Twenty-five women who were 6 weeks postpartum were given a single injection of 150 mg of depot medroxyprogesteroneacetate. Serum prolactin levels were compared to those of 25 women who used an IUD. All women breastfed their infants to about the same extent. Basal serum prolactin levels were similar between the groups at the beginning of the study. These levels slowly decreased in the IUD group, but increased in the medroxyprogesterone group. The differences were statistically significant at 6 weeks after the start of the study. Basal prolactin increases in the medroxyprogesterone were 14% over baseline and 59% over the IUD group at 6 weeks.
Women (n = 80) were assigned randomly to receive intramuscular depot medroxyprogesteroneacetate(DMPA) 250 mg 1 to 2 days postpartum. Other women in the study (n = 616) were started on DMPA at 30 days postpartum. The median duration of lactation in both groups was longer in these women than the lactation duration following previous births.
A nonrandomized, nonblinded study compared women who received either nonhormonal contraception (n = 56) or depot medroxyprogesteroneacetate(n = 47) 150 mg intramuscularly upon discharge from the hospital. No statistical differences were found in the breastfeeding rates or percentage of women exclusively breastfeeding between the 2 groups of women at 1, 4, 8, 12 or 16 weeks postpartum.
In a nonrandomized, nonblinded study comparing women who were breastfeeding at discharge, 102 postpartum women received depot medroxyprogesteroneacetate(dosage not stated) in the early postpartum period (average 51.9 hours postpartum; range 6.25 to 132 hours), 181 received another progestin-only contraceptive and 138 used nonhormonal contraception. No differences in breastfeeding rates were seen at 2 and 6 weeks, but women receiving any hormonal contraceptive were breastfeeding at a lower rate (72.1% vs 77.6%) at 4 weeks postpartum. The authors concluded that progestin-only contraception initiated in the early postpartum period had no adverse effects on breastfeeding rates.
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